ABSTRACT
Ligand-based virtual screening (LBVS) can be pivotal for identifying potential drug leads, especially when the target protein's structure is unknown. However, current LBVS methods are limited in their ability to consider the ligand conformational flexibility. This study presents AutoDock-SS (Similarity Searching), which adapts protein-ligand docking for use in LBVS. AutoDock-SS integrates novel ligand-based grid maps and AutoDock-GPU into a novel three-dimensional LBVS workflow. Unlike other approaches based on pregenerated conformer libraries, AutoDock-SS's built-in conformational search optimizes conformations dynamically based on the reference ligand, thus providing a more accurate representation of relevant ligand conformations. AutoDock-SS supports two modes: single and multiple ligand queries, allowing for the seamless consideration of multiple reference ligands. When tested on the Directory of Useful DecoysâEnhanced (DUD-E) data set, AutoDock-SS surpassed alternative 3D LBVS methods, achieving a mean AUROC of 0.775 and an EF1% of 25.72 in single-reference mode. The multireference mode, evaluated on the augmented DUD-E+ data set, demonstrated superior accuracy with a mean AUROC of 0.843 and an EF1% of 34.59. This enhanced performance underscores AutoDock-SS's ability to treat compounds as conformationally flexible while considering the ligand's shape, pharmacophore, and electrostatic potential, expanding the potential of LBVS methods.
Subject(s)
Molecular Docking Simulation , Ligands , Drug Evaluation, Preclinical/methods , Proteins/chemistry , Proteins/metabolism , User-Computer Interface , Protein Conformation , Molecular ConformationABSTRACT
We present one of the earliest domestic mpox cases in Taiwan, highlighting the asynchronous and atypical progression of cutaneous lesions which could pose significant diagnostic challenges for clinicians.
Subject(s)
Mpox (monkeypox) , Humans , Patients , Disease Progression , TaiwanABSTRACT
Gastropericardial fistula is a rare but lethal condition. Several etiologies have been reported, including previous gastric or esophageal surgery, malignancy, trauma, infection, and ulcer perforation. Typical symptoms included chest pain, epigastric pain, fever and dyspnea. Gastropericardial fistula can lead to serious complications, including cardiac tamponade, sepsis, hemodynamic compromise and death. Therefore, early diagnosis and timely management are important for physicians to prevent from catastrophic complications. Here, we present a case of a man who presented with acute purulent pericarditis secondary to a gastropericardial fistula to highlight the pathogenesis and suggest therapeutic strategies.
